Making mice live longer, then humans

Invariably, everyone gets old. However, as a true testament to human stubbornness, research toward a “cure” for aging has never stopped. Over the past few decades, various approaches have allowed scientists to generate animal models with extended lifespans. In recent years, this trend has moved from lower organisms to mammalian model systems. There are now several rodent models with enhanced longevity. Many of these models are directly relevant to human aging.

A new study has identified a deletion in exon 3 of human growth hormone receptor (GHR) to be prevalent in naturally long-lived men1. The presence of two copies of this mutation may allow men to live about ten years longer than they otherwise would. This agrees with many findings from rodent models. Transgenic mice that overexpress GH age rapidly, while knockout mice lacking GHR are long-lived2,3. In humans and mice, IGF1 signaling is also closely linked to longevity via a signaling pathway overlapping that of GH4,5.

Pathways involved in managing oxidative stress have also been implicated in mammalian aging. Deletion of the proapoptotic gene p66Shc has been shown to significantly extend longevity in mice, and ectopic targeting of catalase to mitochondria in transgenic mice leads to reduction of many age-associated health issues6, 7.

Some other mouse models with increased longevity include knockout of type 5 adenylyl cyclase, which increases median lifespan by 30%, and knockout of the RIIβ isoform of PKA, which extends male mouse longevity and increases age-related health8, 9.

In the coming years, there will likely be even more progress in lifespan extension, perhaps even including direct applications to humans.